The leading major causes of blindness in the U.S. are exudative age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR). Both are due to aberrant neovascularization in the eye. PEDF (Pigment Epithelium-Derived Factor) is a potent endogenous antiangiogenic/neurotrophic factor and is considered a key regulator of vascularity in the eye. Compelling data from a variety of investigators indicates that PEDF can inhibit neovascularization in models of human disease. For this SBIR, we hypothesize that direct administration of PEDF protein could be used to treat blinding ocular neovascular diseases such as wet AMD as well as other ocular disorders. Therefore, it is the overall goal of this SBIR Phase II to generate preclinical data enabling clinical testing of PEDF protein. The Specific Aims accordingly are: 1) To test the efficacy of purified human PEDF protein, generated during the SBIR Phase I funded period, in an in vivo experimental ocular disease model; 2) To determine if prolonging PEDF concentrations within the eye by pegylation of PEDF will result in enhanced antiangiogenic activity; and 3) To further advance PEDF protein production/purification methods and assays in preparation of clinical grade material. The results of these studies will be used to decide whether clinical testing of PEDF protein is warranted and if so, provide critical components of the data package necessary for an IND submission.